Hellekant Pituitary Flashcards
Growth hormone is produced by what cells?
Somatotrophs
Prolactin is produced by what type of cells?
Mammotrophs
What hormones are produced by acidophils?
Growth hormone and prolactin
What effect does TRH have on prolactin?
Promotes release of prolactin
What effect does somatostatin have on growth hormone?
Inhibition
What effect does dopamine have on Growth hormone?
Inhibits GH release
What kind of receptor is GHRH receptor?
GPCR - stimulate adenylyl cyclase
What type of receptor are the somatostatin receptors?
Gi
What type of receptor are the GH receptors?
Transmembrane on target cells - activate JAK/STAT
When growth hormone acts on the liver, what happens?
The liver produces insulin-like growth factor - 1
What are the actions of growth hormone?
Promotes muscle mass and longitudinal (linear) bone growth, can cause hyperglycemia, increases mobilization of fats; acts on liver to increase release of IGF-1
How is the growth hormone receptor binding protein produced?
Proteolysis of GHR at the cell surface; thereby releasing its extracellular domain
What effects does IGF-1 have?
Increases cartilage growth
Severe GH deficiency in children leads to what?
Proportional dwarfism
What is the pathogenesis behind proportional dwarfism?
Severe GH deficiency
What is Laron syndrome?
AR GHR variant with insensitivy to GH; imparts resistance to CA and DM and prolongs life
What condition is caused by gene mutation in the GH receptor, resulting in insensitivity to GH?
Laron syndrome
What are the symptoms of GH def in adults?
Generalized obesity, reduced muscle mass, asthenia, reduced cardiac output
What does the insulin tolerance test tell you?
Give insulin, create hypoglycemia, and should see increased cortisol from the adrenals, and increased GH from anterior pituitary; failure to respond may suggest need for GH or glucocorticoids
What is sermorelin?
GHRH analog
What tests can be used to assess GH deficiency?
Insulin tolerance test or GHRH analog and arginine co-stimulation test
How is the arginine GHRH test done?
Inject arginine over 30 minutes, inject GHRH over 1 minute, measure serum GH over the next hour; should see GH > 8, if less suggests GH def
What is the mot common pituitary hormone deficiency in children?
Growth hormone
What is an early sign of GH deficiency in children?
Hypoglycemia - due to unopposed action of insulin
What are the therapeutic uses of GH in adults?
GH def, wasting in patients with HIV, short bowel syndrome
Why is GH used in short bowel syndrome in patients receiving specialized nutrition support?
Improved mucousal integrity and thus GI function
What is somatropin?
Recombinant human growth hormone
When using rhGH in adults, what labs should be monitored?
Lipid profile, fasting glucose, bone density
In Laron-type dwarfism, low levels of what are seen?
IGF-1; GH does not have effect on GHR on liver
What is mecasermin?
Aka increlex = rh IGF-1
What is mecasermin rinfabate?
Complex of rhIGF-1 + IGFBP3
What is Iplex?
Mecasermin rinfabate - complex of rhIGF-1 + IGFBP3
What are the drug names for rhIGF?
Mecasermin (increlex) or mecasermin rinfabate (iplex)
What is IGFBP3?
IGF carrier protein
When should rhIGF be avoided?
Children with cancer; in patients with closed epiphyses
Hypersecretion of GH in adults is most commonly due to what?
GH secreting anterior pituitary adenoma
Abnormal growth of what tissues is seen in hypersecretion of GH?
Abnormal growth of cartilage, bone, skin, muscle, heart, liver, GI
What is usually first indication of GH hypersecretion?
Elevated IGF-1
How is GH hypersecretion confirmed?
Elevated GH level 2 hours after glucose administration
During sleep, how does a patient with acromegaly differ from a “normal” patient?
GH levels do not show circadian rhythm or peaks and nadirs, but are within normal range
How is GH hypersecretion treated?
GH inhibitory hormones: somatostatin and dopamine
What dopamine receptor is targeted in treatment of GH adenoma?
D2
What is octreotide?
Somatostatin analog (long acting)
What is pegvisomant?
PEG derivative of mutant GH; binds GH receptor and blocks downstream events
What is one of the problems encountered when using pegvisomant?
Blocks GHR on liver, decreasing IGF-1 release, but then increasing GH secretion due to loss of negative feedback
What drug is a GH antagonist?
Pegvisomant
What dopamine analogs are used in the treatment of pituitary adenoma that is secreting prolactin/growth hormone?
Bromocriptine and cabergoline
What is the MOA of bromocriptine?
Dopamine analog at D2 receptor
What is the MOA of cabergoline?
Dopamine analog at D2
What effect does VIP have on prolactin?
Promotes release
What effect does TRH have on prolactin?
Promotes release
What is the primary inhibitor of prolactin release?
Dopamine
What do mammotrophs produce?
Prolactin
What type of receptor does prolactin bind?
Transmembrane proteins that activate JAK/STAT family; tyrosine kinase
What form of the prolactin receptor is the active form?
Long form
What form of the prolactin receptor is acts as a dominant negative form?
Short form
What are the physiologic effects of prolactin?
Breast development during pregnancy, milk secretion during lactation
What effect does prolactin have on breast tissue?
Expansion of lobular-alveolar development during pregnancy
During pregnancy, what is inhibiting lactation?
High levels of progesterone
Hypersecretion of prolactin in males results in what?
Impotence
Hypersecretion of prolactin has what effects on hormones?
Inhibits GnRH, and therefore decreases gonadal hormones
What is the preferred treatment of prolactinoma?
Cabergoline - dopamine agonist; high efficacy
What receptors are targeted in treatment of prolactinoma?
D2
